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https://www.readbyqxmd.com/read/29126768/increased-functional-coupling-of-5-ht1a-autoreceptors-to-girk-channels-in-tph2-mice
#1
Boris Mlinar, Alberto Montalbano, Jonas Waider, Klaus-Peter Lesch, Renato Corradetti
Firing activity of serotonergic neurons is under regulatory control by somatodendritic 5-HT1A autoreceptors (5-HT1AARs). Enhanced 5-HT1AAR functioning may cause decreased serotonergic signaling in brain and has thereby been implicated in the etiology of mood and anxiety disorders. Tryptophan hydroxylase-2 knockout (Tph2(-/-)) mice exhibit sensitization of 5-HT1A agonist-induced inhibition of serotonergic neuron firing and thus represents a unique animal model of enhanced 5-HT1AAR functioning. To elucidate the mechanisms underlying 5-HT1AAR supersensitivity in Tph2(-/-) mice, we characterized the activation of G protein-coupled inwardly-rectifying potassium (GIRK) conductance by the 5-HT1A receptor agonist 5-carboxamidotryptamine using whole-cell recordings from serotonergic neurons in dorsal raphe nucleus...
November 7, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29046318/central-serotonin-and-the-control-of-arterial-blood-pressure-and-heart-rate-in-infant-rats-influence-of-sleep-state-and-sex
#2
Jennifer L Magnusson, Kevin James Cummings
Sudden Infant Death Syndrome (SIDS) is associated with serotonin (5-HT) neuron abnormalities. There is evidence of autonomic dysfunction during sleep in infants eventually succumbing to SIDS, as well as cardiovascular collapse prior to death. Neonatal rodents deficient in central 5-HT display hypotension and bradycardia. We hypothesized that central 5-HT reduces cardiac vagal tone and increases sympathetic vascular tone and, given the firing pattern of 5-HT neurons, that these effects are greater in quiet sleep (QS) than in active sleep (AS)...
October 18, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/29035515/isoform-specific-substrate-inhibition-mechanism-of-human-tryptophan-hydroxylase
#3
Kasper D Tidemand, Günther H Peters, Pernille Harris, Eva Stensgaard, Hans E M Christensen
Tryptophan hydroxylase (TPH) catalyzes the initial and rate-limiting step in the biosynthesis of serotonin, which is associated with a variety of disorders such as depression and irritable bowel syndrome. TPH exists in two isoforms: TPH1 and TPH2. TPH1 catalyzes the initial step in the synthesis of serotonin in the peripheral tissues, while TPH2 catalyzes this step in the brain. In this study, the steady-state kinetic mechanism for the catalytic domain of human TPH1 has been determined. Varying substrate tryptophan (Trp) and tetrahydrobiopterin (BH4) results in a hybrid Ping Pong-ordered mechanism in which the reaction can either occur through a Ping Pong or a sequential mechanism depending on the concentration of tryptophan...
October 27, 2017: Biochemistry
https://www.readbyqxmd.com/read/28972592/genetically-driven-brain-serotonin-deficiency-facilitates-panic-like-escape-behavior-in-mice
#4
J Waider, S Popp, M D Lange, R Kern, J F Kolter, J Kobler, N C Donner, K R Lowe, J H Malzbender, C J Brazell, M R Arnold, B Aboagye, A Schmitt-Böhrer, C A Lowry, H C Pape, K P Lesch
Multiple lines of evidence implicate brain serotonin (5-hydroxytryptamine; 5-HT) system dysfunction in the pathophysiology of stressor-related and anxiety disorders. Here we investigate the influence of constitutively deficient 5-HT synthesis on stressor-related anxiety-like behaviors using Tryptophan hydroxylase 2 (Tph2) mutant mice. Functional assessment of c-Fos after associated foot shock, electrophysiological recordings of GABAergic synaptic transmission, differential expression of the Slc6a4 gene in serotonergic neurons were combined with locomotor and anxiety-like measurements in different contextual settings...
October 3, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28968985/stress-inhibits-tryptophan-hydroxylase-expression-in-a-rat-model-of-depression
#5
Yi Chen, Haixia Xu, Mingyue Zhu, Kun Liu, Bo Lin, Ruxian Luo, Chuanbai Chen, Mengsen Li
Serotonin (5-hydroxytryptamine, 5-HT) dysfunction is associated with the pathophysiology of depression. Tryptophan hydroxylase (TPH), the rate-limiting enzyme in 5-HT biosynthesis, is believed to have essential role in many mental disorders, including depression. In the present study, we generated a rat model of depression by exposing the animals to stress, and the rats were then treated with paroxetine. The results indicated that the concentration of 5-HT in the brain and liver tissues were significantly lower in the rat model of depression than in healthy or treated rats...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28933662/deficiency-of-serotonin-in-raphe-neurons-and-altered-behavioral-responses-in-tryptophan-hydroxylase-2-knockout-medaka-oryzias-latipes
#6
Satoshi Ansai, Hiroshi Hosokawa, Shingo Maegawa, Kiyoshi Naruse, Youhei Washio, Kenji Sato, Masato Kinoshita
Serotonin (5-hydroxytryptamine [5-HT]) is a bioactive monoamine that acts as a neurotransmitter in the central and peripheral nervous system of animals. Teleost fish species have serotonergic neurons in the raphe nuclei of the brainstem; however, the role of 5-HT in the raphe neurons in teleost fish remains largely unknown. Here, we established a medaka (Oryzias latipes) strain with targeted disruption of tryptophan hydroxylase 2 (tph2) gene that is involved in the 5-HT synthesis in the raphe nuclei. Immunohistochemistry and mass spectrometry analysis revealed that the homozygous mutants (tph2(Δ13/Δ13)) lacked the ability to synthesize 5-HT in the raphe neurons...
September 21, 2017: Zebrafish
https://www.readbyqxmd.com/read/28902619/a-case-control-association-study-of-12-candidate-genes-and-attempted-suicide-in-french-adolescents
#7
Bojan Mirkovic, David Cohen, Claudine Laurent, Malaika Lasfar, Christophe Marguet, Prsicille Gerardin
Background Suicide is the second leading cause of death for 10-19-year-olds. Evidence has shown that attempted suicide is a complex interplay of genes and environmental factors. In the adult population, possible associations between genetic polymorphisms and suicidal behaviors have been investigated for several genes, most often with inconsistent findings and poor replicability of significant associations. This study aimed to identify gene variants conferring risk for adolescent suicide attempt. Methods We selected the genes and variants after an analysis of the literature and a selection of the most significant associations identified...
September 13, 2017: International Journal of Adolescent Medicine and Health
https://www.readbyqxmd.com/read/28888667/preimmunization-with-a-heat-killed-preparation-of-mycobacterium-vaccae-enhances-fear-extinction-in-the-fear-potentiated-startle-paradigm
#8
James H Fox, James E Hassell, Philip H Siebler, Mathew R Arnold, Andrew K Lamb, David G Smith, Heidi E W Day, Tessa M Smith, Emma M Simmerman, Alexander A Outzen, Kaley S Holmes, Christopher J Brazell, Christopher A Lowry
The hygiene hypothesis or "Old Friends" hypothesis proposes that inflammatory diseases are increasing in modern urban societies, due in part to reduced exposure to microorganisms that drive immunoregulatory circuits, and a failure to terminate inappropriate inflammatory responses. Inappropriate inflammation is also emerging as a risk factor for trauma-related, anxiety, and affective disorders, including posttraumatic stress disorder (PTSD), which is characterized as persistent re-experiencing of the trauma after a traumatic experience...
September 6, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28866660/generation-of-tryptophan-hydroxylase-2-gene-knockout-pigs-by-crispr-cas9-mediated-gene-targeting
#9
Ze Li, Hai-Yuan Yang, Ying Wang, Man-Ling Zhang, Xiao-Rui Liu, Qiang Xiong, Li-Ning Zhang, Yong Jin, Li-Sha Mou, Yan Liu, Rong-Feng Li, Yi Rao, Yi-Fan Dai
Unbalanced brain serotonin (5-HT) levels have implications in various behavioral abnormalities and neuropsychiatric disorders. The biosynthesis of neuronal 5-HT is regulated by the rate-limiting enzyme, tryptophan hydroxylase-2 (TPH2). In the present study, the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (Cas) system was used to target theTph2 gene in Bama mini pig fetal fibroblasts. It was found that CRISPR/Cas9 targeting efficiency could be as high as 61.5%, and the biallelic mutation efficiency reached at 38...
September 26, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28856708/degeneration-of-serotonin-neurons-triggers-spasticity-in-amyotrophic-lateral-sclerosis
#10
Hajer El Oussini, Jelena Scekic-Zahirovic, Pauline Vercruysse, Christine Marques, Sylvie Dirrig-Grosch, Stéphane Dieterlé, Gina Picchiarelli, Jérôme Sinniger, Caroline Rouaux, Luc Dupuis
OBJECTIVE: Spasticity occurs in a wide range of neurological diseases, including neurodegenerative diseases, after trauma, and after stroke, and is characterized by increased reflexes leading to muscle hypertonia. Spasticity is a painful symptom and can severely restrict everyday life, but might also participate in maintaining a low level of motor function in severely impaired patients. Constitutive activity of the serotonin receptors 5-HT2B/C is required for the development of spasticity after spinal cord injury and during amyotrophic lateral sclerosis (ALS)...
September 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28775068/active-sleep-unmasks-apnea-and-delayed-arousal-in-infant-rat-pups-lacking-central-serotonin
#11
Jacob O Young, Aron Geurts, Matthew R Hodges, Kevin J Cummings
Sudden infant death syndrome (SIDS), occurring during sleep periods, is highly associated with abnormalities within serotonin (5-HT) neurons, including reduced 5-HT. There is evidence that future SIDS cases experience more apnea and have abnormal arousal from sleep. In rodents, a loss of 5-HT neurons is associated with apnea in early life and, in adulthood, delayed arousal. As the activity of 5-HT neurons changes with vigilance state, we hypothesized that the degree of apnea and delayed arousal displayed by rat pups specifically lacking central 5-HT varies with state...
October 1, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28769763/development-of-serotonergic-fibers-in-the-post-natal-mouse-brain
#12
Giacomo Maddaloni, Alice Bertero, Marta Pratelli, Noemi Barsotti, Annemarie Boonstra, Andrea Giorgi, Sara Migliarini, Massimo Pasqualetti
Serotonin (5-HT)-synthetizing neurons, which are confined in the raphe nuclei of the rhombencephalon, provide a pervasive innervation of the central nervous system (CNS) and are involved in the modulation of a plethora of functions in both developing and adult brain. Classical studies have described the post-natal development of serotonergic axons as a linear process of terminal field innervation. However, technical limitations have hampered a fine morphological characterization. With the advent of genetic mouse models, the possibility to label specific neuronal populations allowed the rigorous measurement of their axonal morphological features as well as their developmental dynamics...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28751217/human-placenta-expresses-both-peripheral-and-neuronal-isoform-of-tryptophan-hydroxylase
#13
Laetitia Laurent, Kathy Deroy, Joey St-Pierre, Francine Côté, J Thomas Sanderson, Cathy Vaillancourt
The role of placental serotonin has been an active topic of research notably because of its crucial role in brain development. However, which cell types synthesize serotonin in human placenta remains unknown. Moreover, it is not known if the two tryptophan hydroxylase isoforms (TPH1 and TPH2), the rate-limiting enzymes in serotonin biosynthesis, are expressed in placenta. Human placentas were obtained in first trimester or at term, and trophoblast cells were isolated and purified using a magnetic cell sorter and placed in primary culture...
September 2017: Biochimie
https://www.readbyqxmd.com/read/28719094/discovery-and-characterization-of-a-novel-tryptophan-hydroxylase-1-inhibitor-as-a-prodrug
#14
Hailong Shi, Yaya Cui, Yifei Qin
Serotonin (5-HT) is an important neurotransmitter and paracrine signaling molecule in the gastrointestinal tract. Two distinct tryptophan hydroxylases (TPH), TPH1 and TPH2 are the rate-limiting enzymes in the 5-HT biosynthesis process. TPH1 expression is mainly limited in the enterochromaffin cells and distributed in peripheries such as the skin and gut, while TPH2 is the predominant isoform in the CNS. In this study, mol002291 was screened as a drug-like compound from the TCM database for the inhibitor of TPH...
July 18, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28716530/genetic-association-analysis-of-serotonin-and-signal-transduction-pathways-in-suicide-attempters-from-an-italian-sample-of-psychiatric-patients
#15
Maurizio Pompili, Giovanna Gentile, Catia Scassellati, Cristian Bonvicini, Marco Innamorati, Denise Erbuto, Franco Montebovi, Giuseppe Ducci, Alberto Forte, Eleonora De Pisa, Stefano Ferracuti, Gianluca Serafini, Vincenzo De Luca, Mario Amore, Maurizio Simmaco, Paolo Girardi
Genetic factors have been reported to contribute to the liability of suicide. We aimed to investigate functional polymorphisms in eight genes (serotonin transporter, SLC6A4; receptors, 5HTR1A, 1B, 5HTR2A; Tryptophan Hydroxylase, TPH1, TPH2; Monoamine Oxidase, MAOA and G Protein Subunit Beta 3, GNB3) to investigate their predictive value for suicide. The possible confounding effects of gender and phenotypic patients dissection were also valued. A sample of 111 consecutive psychiatric inpatients was recruited and assessed using specific psychometric instruments...
July 14, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28706142/stress-inhibits-tryptophan-hydroxylase-expression-in-a-rat-model-of-depression
#16
Yi Chen, Haixia Xu, Mingyue Zhu, Kun Liu, Bo Lin, Ruxian Luo, Chuanbai Chen, Mengsen Li
Serotonin (5-hydroxytryptamine, 5-HT) dysfunction is associated with the pathophysiology of depression. Tryptophan hydroxylase (TPH), the rate-limiting enzyme in 5-HT biosynthesis, is believed to have essential role in many mental disorders, including depression. In the present study, we generated a rat model of depression by exposing the animals to stress, and the rats were then treated with paroxetine. The results indicated that the concentration of 5-HT in the brain and liver tissues were significantly lower in the rat model of depression than in healthy or treated rats...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28687505/xiaochaihutang-attenuates-depressive-anxiety-like-behaviors-of-social-isolation-reared-mice-by-regulating-monoaminergic-system-neurogenesis-and-bdnf-expression
#17
Jie Ma, Fang Wang, Jingyu Yang, Yingxu Dong, Guangyue Su, Kuo Zhang, Xing Pan, Ping Ma, Tingshuo Zhou, Chunfu Wu
ETHNOPHARMACOLOGICAL RELEVANCE: Xiaochaihutang (XCHT), as a classical herbal formula for the treatment of "Shaoyang syndrome" has been demonstrated to exert an antidepressant effect in multiple animal models of depression as shown in our previous studies. However, the effects of XCHT on social isolation (SI)-reared mice have not been investigated. This study aims to explore the effects of XCHT on depressive/anxiety-like behaviors of SI-reared mice, and its implicated mechanisms, including alterations in the monoaminergic system, neurogenesis and neurotrophin expression...
July 5, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28650979/expression-of-cerebral-serotonin-related-to-anxiety-like-behaviors-in-c57bl-6-offspring-induced-by-repeated-subcutaneous-prenatal-exposure-to-low-dose-lipopolysaccharide
#18
Pei-Tan Hsueh, Hsuan-Han Wang, Chiu-Lin Liu, Wei-Fen Ni, Ya-Lei Chen, Jong-Kang Liu
Prenatal exposure to lipopolysaccharide (LPS), which likely occurs due to infection or contact with environmental allergens during pregnancy, is a proposed risk factor that induces anxiety- and autism spectrum disorder-like behaviors in offspring. However, the molecular and behavioral changes in offspring after maternal immune activation have not been completely identified. We hypothesized that a subcutaneous injection of LPS in a pregnant mouse would induce changes in cerebral serotonin (5-HT) in parallel to the appearance of anxiety-like behaviors in the dam's offspring...
2017: PloS One
https://www.readbyqxmd.com/read/28630479/attention-cognitive-control-and-motivation-in-adhd-linking-event-related-brain-potentials-and-dna-methylation-patterns-in-boys-at-early-school-age
#19
Hartmut Heinrich, Juliane Grunitz, Valeska Stonawski, Stefan Frey, Simone Wahl, Björn Albrecht, Tamme W Goecke, Matthias W Beckmann, Johannes Kornhuber, Peter A Fasching, Gunther H Moll, Anna Eichler
In order to better understand the underpinnings of attention-deficit/hyperactivity disorder (ADHD), we targeted the relationship of attentional, cognitive control and motivational processes with DNA methylation patterns of 60 candidate genes in boys at early school age. Participants (6 to 8 years; N = 82) were selected from a German longitudinal cohort (FRANCES). ADHD-related behaviour was assessed via maternal ratings. Performance and event-related potential measures (inter alia Cue-P3 and Nogo-P3), which were recorded in a motivational go/nogo task, indicated diminished attentional orienting, reduced inhibitory response control and a larger motivational effect on performance in ADHD already at this relatively young age...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28590957/genetic-moderation-of-cocaine-subjective-effects-by-variation-in-the-tph1-tph2-and-slc6a4-serotonin-genes
#20
Michelle A Patriquin, Sara C Hamon, Mark J Harding, Ellen M Nielsen, Thomas F Newton, Richard De La Garza, David A Nielsen
OBJECTIVE: This study investigated variants of tryptophan hydroxylase (TPH)1, TPH2, and SLC6A4 in the moderation of the subjective effects of cocaine. METHODS: Non-treatment-seeking cocaine-dependent individuals (N=66) were intravenously administered saline and cocaine (40 mg) in a randomized order. Participants self-reported subjective effects of cocaine using a visual analog scale starting before administration of saline or cocaine (-15 min) to up to 20 min after infusion...
October 2017: Psychiatric Genetics
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